Antibodies against OX-40 and uses thereof

Abstract

Provided herein are antibodies, or antigen binding portions thereof, that bind to OX40. Also provided are uses of these proteins in therapeutic applications, such as in the treatment of cancer. Further provided are cells that produce the antibodies, polynucleotides encoding the heavy and/or light chain variable region of the antibodies, and vectors comprising the polynucleotides encoding the heavy and/or light chain variable region of the antibodies.

The invention claimed is: 
     
       1. A method of stimulating an antigen-specific T cell response comprising contacting an antigen-specific T cell with an isolated antibody that binds to human OX40 (“anti-OX40 antibody”), such that an antigen-specific T cell response is stimulated, and wherein the anti-OX40 antibody comprises
 a heavy chain variable region CDR1 comprising the sequence of SEQ ID NO: 87, a heavy chain variable region CDR2 comprising the sequence of SEQ ID NO: 317, and a heavy chain variable region CDR3 comprising the sequence of SEQ ID NO: 89, and a light chain variable region CDR1 comprising the sequence of SEQ ID NO: 90, a light chain variable region CDR2 comprising the sequence of SEQ ID NO: 91, and a light chain variable region CDR3 comprising the sequence of SEQ ID NO: 92. 
 
     
     
       2. A method of reducing or depleting the number of T regulatory cells in a tumor of a subject in need thereof comprising administering to the subject a therapeutically effective amount of an isolated antibody that binds to human OX40 (“anti-OX40 antibody”), such that the number of T regulatory cells is reduced or depleted, and wherein the anti-OX40 antibody comprises
 a heavy chain variable region CDR1 comprising the sequence of SEQ ID NO: 87, a heavy chain variable region CDR2 comprising the sequence of SEQ ID NO: 317, and a heavy chain variable region CDR3 comprising the sequence of SEQ ID NO: 89, and a light chain variable region CDR1 comprising the sequence of SEQ ID NO: 90, a light chain variable region CDR2 comprising the sequence of SEQ ID NO: 91, and a light chain variable region CDR3 comprising the sequence of SEQ ID NO: 92. 
 
     
     
       3. A method of inhibiting the growth of tumor cells in a subject in need thereof comprising administering to the subject a therapeutically effective amount of an isolated antibody that binds to human OX40 (“anti-OX40 antibody”), such that the growth of tumor cells is inhibited, and wherein the anti-OX40 antibody comprises
 a heavy chain variable region CDR1 comprising the sequence of SEQ ID NO: 87, a heavy chain variable region CDR2 comprising the sequence of SEQ ID NO: 317, and a heavy chain variable region CDR3 comprising the sequence of SEQ ID NO: 89, and a light chain variable region CDR1 comprising the sequence of SEQ ID NO: 90, a light chain variable region CDR2 comprising the sequence of SEQ ID NO: 91, and a light chain variable region CDR3 comprising the sequence of SEQ ID NO: 92. 
 
     
     
       4. The method of  claim 1 , wherein the anti-OX40 antibody comprises
 a heavy chain variable region comprising the sequence of SEQ ID NO: 318 and a light chain variable region comprising the sequence of SEQ ID NO: 94. 
 
     
     
       5. The method of  claim 2 , wherein the anti-OX40 antibody comprises
 a heavy chain variable region comprising the sequence of SEQ ID NO: 318 and a light chain variable region comprising the sequence of SEQ ID NO: 94. 
 
     
     
       6. The method of  claim 3 , wherein the anti-OX40 antibody comprises
 a heavy chain variable region comprising the sequence of SEQ ID NO: 318 and a light chain variable region comprising the sequence of SEQ ID NO: 94. 
 
     
     
       7. The method of  claim 1 , wherein the anti-OX40 antibody comprises
 a heavy chain comprising the sequence of SEQ ID NO: 124 and a light chain comprising the sequence of SEQ ID NO: 116. 
 
     
     
       8. The method of  claim 2 , wherein the anti-OX40 antibody comprises
 a heavy chain comprising the sequence of SEQ ID NO: 124 and a light chain comprising the sequence of SEQ ID NO: 116. 
 
     
     
       9. The method of  claim 3 , wherein the anti-OX40 antibody comprises
 a heavy chain comprising the sequence of SEQ ID NO: 124 and a light chain comprising the sequence of SEQ ID NO: 116. 
 
     
     
       10. The method of  claim 1 , wherein the contacting is performed in vitro. 
     
     
       11. The method of  claim 1 , wherein the contacting is performed in a subject in vivo. 
     
     
       12. The method of  claim 1 , wherein the antigen-specific T cell comprises an effector T cell (Teff cell), helper T cell (Th cell), cytotoxic T cell (T c  cell), or combinations thereof. 
     
     
       13. The method of  claim 11 , wherein the subject has a cancer. 
     
     
       14. The method of  claim 11 , comprising administering one or more additional therapeutics to the subject. 
     
     
       15. The method of  claim 14 , wherein the one or more additional therapeutics comprise an anti-PD-1 antibody, an anti-PD-L1 antibody, an anti-LAG-3 antibody, an anti-CTLA-4 antibody, anti-TGFβ antibody, or combinations thereof. 
     
     
       16. The method of  claim 2 , comprising administering one or more additional therapeutics to the subject. 
     
     
       17. The method of  claim 16 , wherein the one or more additional therapeutics comprise an anti-PD-1 antibody, an anti-PD-L1 antibody, an anti-LAG-3 antibody, an anti-CTLA-4 antibody, anti-TGFβ antibody, or combinations thereof. 
     
     
       18. The method of  claim 3 , comprising administering one or more additional therapeutics to the subject. 
     
     
       19. The method of  claim 18 , wherein the one or more additional therapeutics comprise an anti-PD-1 antibody, an anti-PD-L1 antibody, an anti-LAG-3 antibody, an anti-CTLA-4 antibody, anti-TGFβ antibody, or combinations thereof.